Project Summary/Abstract This project aims to develop an automated system for reproducible high-yield pancreatic islet isolation, to greatly improve islet transplantation and benefit patients who suffer type I diabetes (T1D). The new system will use state-of-the-art technologies ? CG Scientific?s patent-pending automated cell isolation platform (ACIP) and its proprietary ?no islet left behind? (NILB) process ? to replace the nearly 30-year- old Ricordi apparatus and achieve high islet recovery, viability, function and reproducibility. The automated system will enable standardized islet isolation, and facilitate islet isolation at local laboratories to drastically reduce the damaging cold ischemic time, thereby providing islets of higher quantity and quality. These improvements will potentially allow many donor pancreata ? which would otherwise be disqualified due to poor quality ? to be used for islet transplantation, thereby significantly reducing the cost of islet transplantation and potentially enabling single-donor islet transplantation to become a standard therapy. In collaboration with Dr. Harlan, former Head of the Diabetes Branch at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Drs. Greiner and Bortell, the original developers of the gold-standard diabetic NRG-Akita mouse model, CG Scientific has demonstrated that its technologies can potentially increase islet recovery by ~2.5x. Phase I of this project specifically aims to develop a scaled-up prototype device for automated islet isolation, benchmark against current standards, demonstrate its superior performance, and validate the ex vivo and in vivo functions of the isolated islets, using porcine pancreata as the model system. The successful completion of this project will result in the commercialization of a standardized, automated and high-yield islet isolation system ? the first modern islet isolation system ? that accelerates diabetes research and standardizes single-donor islet transplantation, thereby benefiting the 1.3 million people in the United States and the over 40 million people worldwide who suffer T1D.